title: Synthesis and evaluation of the cell cycle arrest and CT DNA interaction properties of 4β-amino-4'-O-demethyl-4-deoxypodophyllotoxins.
abstract: A series of 4β-amino-4'-O-demethyl-4-deoxypodophyllotoxin derivatives were synthesized, and their cytotoxicities against several human cancer cell lines, including HepG2, A549, HeLa and HCT-8 cells, evaluated. Some of these compounds exhibited higher levels of cytotoxicity than the anticancer drug etoposide. 4β-N-(4-Nitrophenyl piperazinyl)-4'-O-demethyl-4-deoxypodophyllotoxin (11) was found to be the most potent synthesized compound in the current study, and induced cell cycle arrest in the G2/M phase in HeLa cells, which was accompanied by apoptosis. Furthermore, this compound activated the expression of cdc2, cyclin B1, p53 and caspase-3 in HeLa cells, leading to changes in the conformation of calf thymus DNA from the B-form to a more compact C-form.
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Jian-Fei
authors.initials: JF
authors.lastname: Liu
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Sang
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Qin
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.forename: Lin
authors.initials: L
authors.lastname: Hui
authors.forename: Yi-Lan
authors.initials: YL
authors.lastname: Ding
authors.forename: Shi-Wu
authors.initials: SW
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002417:Cattle; D045744:Cell Line, Tumor; D056744:Cyclin B1 / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004365:Drugs, Chinese Herbal; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis* / Q000378:metabolism / Q000633:toxicity; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000378:metabolism / Q000633:toxicity; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C588294:4-N-(4-nitrophenylpiperazinyl)-4'-O-demethyl-4-deoxypodophyllotoxin; D000970:Antineoplastic Agents; D056744:Cyclin B1; D004365:Drugs, Chinese Herbal; D010879:Piperazines; D050257:Tubulin Modulators; D016159:Tumor Suppressor Protein p53; C014451:deoxypodophyllotoxin; D004247:DNA; C427203:calf thymus DNA; D016203:CDC2 Protein Kinase; D053148:Caspase 3; D011034:Podophyllotoxin
keywords: Apoptosis; CT DNA; Cell cycle arrest; Demethylepipodophyllotoxin; Podophyllotoxin